Near-infrared (NIR) multi-spectral imaging is a unique tool for characterizing tissue composition in the female breast. The major advantage of this modality is its ability to provide images of tissue oxygen saturation (StO2) as well as total hemoglobin concentration (HbT), water fraction (H2O%) and elastic scattering parameters. Because microcirculation and oxygenation play such major roles in tumor progression and regression, assessing their variation in response to neoadjuvant chemotherapy may reveal early prognostic biomarkers of treatment response that could be used to alter and/or optimize the course of treatment on a more individualized patient basis. Assessing dynamic contrast enhancement in tumor oxygenation after hyperoxic gas inhalation with NIR spectral tomography appears to be feasible and may provide easily- acquired, low cost image signatures for predicting therapeutic response to chemotherapy in the breast. The overall goal of this proposal is to develop and evaluate dynamic NIR tomographic oximetry for characterizing the response of locally advanced breast cancers to neoadjuvant chemotherapy by assessing the temporal variation in tumor oxygenation during hyperoxic gas inhalation. We hypothesize that tumors with initially larger and faster changes before and after breathing 100% oxygen will have better clinical responses to neoadjuvant chemotherapy. This hypothesis will be quantitatively assessed by 1) advancing the current NIR multi-spectral tomography system to image dynamic oxygenation changes within the tumor, induced by breathing 100% oxygen, with a 0.1 Hz image frame rate, 2) quantifying the tumor oxygenation response with respect to hyperoxic inhalation at different times during the course of therapy, and 3) quantifying the pathological and clinical outcomes of response in order to test for correlation with oximetry changes recorded early in the treatment course. Dartmouth College, through the Norris Cotton Cancer Center at the Dartmouth-Hitchcock Medical Center, has significant resources to leverage in order to conduct the proposed study. A group of investigators which includes clinical specialists in diagnostic radiology, surgical oncology, medical oncology, surgical pathology and medical engineering has been configured to develop and evaluate technology for breast imaging for cancer detection, diagnosis and therapy monitoring since 1999. The proposed project is an important component of the research of this group. In addition to the principal investigators, Professor Shudong Jiang and Dr. Peter A. Kaufman, MD, (Medical Oncology), Professors Keith D. Paulsen, Brian W. Pogue and Dr. Wendy A. Wells, MD, (Department of Pathology) will be significant collaborators engaged to accomplish the proposed specific aims, as an adjunct to currently funded grants involving breast imaging research. PUBLIC HEALTH RELEVANCE: This project will develop and evaluate dynamic Near-Infrared (NIR) tomographic oximetry for characterizing the response of locally advanced breast cancers to neoadjuvant chemotherapy by assessing the temporal variation in tumor oxygenation during hyperoxic gas inhalation. NIR oximetry acquired longitudinally during the course of therapy will be correlated with pathological endpoints in order to determine whether early prognostic biomarkers of treatment response can be identified in the dynamic NIR oxygenation signatures that could be used to customize breast cancer treatment decisions to individual patients in the future.